This proposal seeks to establish, for the first time, a Medical Scientist Training Program (MSTP) at the University of North Carolina at Chapel Hill. This new MSTP application is based on a recently reorganized and markedly expanded MD-PhD Program, one that integrates a training experience in clinical medicine with the superb research opportunities available in a wide variety of scientific disciplines at UNC-Chapel Hill. This program is designed to identify the best possible candidates to become physician-scientists, individuals with a wide variety of academic interests who come from broadly diverse backgrounds. In the program, all students are provided with a structured, yet flexible curriculum that is designed to make outstanding opportunities readily available to them. The exception effort of each student is fostered in an environment that includes a critical mass of students with similar goals and aspirations. In addition, each student is supported both financially and emotionally throughout this critical period. We request the funds necessary to support 4 students/year for five years. Funds from this MSTP award, combined with the institutional dollars that have already been committed, will enable us to expand the program to enroll a total of 8 new students/year. Selection of all new students is based upon the excellence of their academic performance, the quality and diversity of their prior research experience, the enthusiasm expressed in their letters of recommendation, and the impressions made during their personal interview. All students enrolled in the UNC MD-PhD Program spend six or more years fulfilling all requirements for both the MD and PhD degrees. Years 1 and 2 are spent in Medical School where they complete both the basic science courses and the more integrated multi- disciplinary courses in human pathophysiology. In addition, they complete formal summer research rotations in any of the participating departments and curricula from the School of Medicine or Public Health on the Health Affairs campus or in Chemistry, Biology, or Computer Science on the Academic Affairs campus. In year 3, the students enter graduate school on a full-time basis where they remain until completion of all PhD requirements. Once the thesis has been successfully written and defended, they then return to medical school and complete their clinical clerkships and the required medical selectives. Credit is given for the PhD research and applied to the remainder of the medial school requirements. With the above changes, we believe that we have now created a model MD-PhD Program. Its continued growth and success will be greatly enhanced by this MSTP award.